Platelet Bioenergetics and Associations With Delirium and Coma in Patients With Sepsis

Chukwudi A. Onyemekwu DO , Niall T. Prendergast MD , Kelly M. Potter PhD , Nicole A. Toney MPH , Mehdi S. Nouraie MD, PhD , Sruti Shiva PhD , Timothy D. Girard MD, MSCI
{"title":"Platelet Bioenergetics and Associations With Delirium and Coma in Patients With Sepsis","authors":"Chukwudi A. Onyemekwu DO ,&nbsp;Niall T. Prendergast MD ,&nbsp;Kelly M. Potter PhD ,&nbsp;Nicole A. Toney MPH ,&nbsp;Mehdi S. Nouraie MD, PhD ,&nbsp;Sruti Shiva PhD ,&nbsp;Timothy D. Girard MD, MSCI","doi":"10.1016/j.chstcc.2024.100076","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis.</p></div><div><h3>Research Question</h3><p>Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis?</p></div><div><h3>Study Design and Methods</h3><p>We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values.</p></div><div><h3>Results</h3><p>Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics.</p></div><div><h3>Interpretation</h3><p>In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.</p></div>","PeriodicalId":93934,"journal":{"name":"CHEST critical care","volume":"2 2","pages":"Article 100076"},"PeriodicalIF":0.0000,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949788424000303/pdfft?md5=9eccba4c611878cb0ee3ee22a907d272&pid=1-s2.0-S2949788424000303-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHEST critical care","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2949788424000303","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background

Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis.

Research Question

Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis?

Study Design and Methods

We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values.

Results

Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics.

Interpretation

In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.

血小板生物能以及与败血症患者谵妄和昏迷的关系
背景脓毒症期间的急性脑功能障碍表现为谵妄或昏迷,这很常见,并与多种不良后果相关,包括机械通气时间延长、住院时间延长和死亡率增加。败血症期间的谵妄和昏迷可能是全身代谢改变的表现。研究问题血小板线粒体生物能的改变是否与脓毒症期间急性脑功能障碍有关? 研究设计与方法我们通过有效的评估方法对重症监护室中的重症患者进行了评估,以确定是否存在谵妄或昏迷。收集并处理血液样本,以分离和测量血小板线粒体耗氧量。我们使用 Seahorse 细胞外通量直接测量基线、质子泄漏、最大耗氧率和细胞外酸化率。结果昏迷患者的最大耗氧量最高,未调整分析中的剩余呼吸容量和细胞外酸化率也最高。在对年龄、镇静剂、改良的器官功能衰竭评估评分(不包括神经系统部分)和原有认知功能进行调整后,剩余呼吸容量的增加仍与昏迷有关。在这项单中心探索性前瞻性队列研究中,我们发现血小板线粒体备用呼吸容量的增加与脓毒症患者的昏迷有关。未来的研究需要确定谵妄与线粒体呼吸生物能之间的关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CHEST critical care
CHEST critical care Critical Care and Intensive Care Medicine, Pulmonary and Respiratory Medicine
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信